title: Keratin 8 is required for the maintenance of architectural structure in thymus epithelium.
abstract: Keratins (Ks), the intermediate filament (IF) proteins of epithelia, are coordinately expressed as pairs in a cell-lineage and differentiation manner. Cortical thymic epithelial cells (cTECs) predominantly express the simple epithelium keratin 8/18 (K8/K18) pair, whereas medullary thymic epithelial cells (mTECs) express the stratified epithelium K5/K14 pair, with TECs exhibiting K5 and K8 at the cortico-medullary junction in mature thymus. In the work reported here, we used wild-type (WT) and K8-knockout (K8-null) mice to address the contribution of K8/K18 IFs in the maintenance of the thymic epithelial structure. K8-null thymus maintained the differential cell segregation at the cortex versus the medulla observed in WT thymus, and the distribution of immature thymocytes at the cortex. The K8/K18 loss did not affect thymocyte development. However, it massively perturbed the TEC morphology both at the cortex and the medulla, along with a prominent depletion of cTECs. Such tissue alterations coincided with an increase in apoptosis and a reduced expression of Albatross (Fas-binding factor-1), also known for its capacity to bind K8/18 IFs. In addition, the K8/K18 loss affected the distribution of K5/K14-positive mTECs, but not their differentiation status. Together, the results indicate that K8/K18 IFs constitute key promoters of the thymic epithelium integrity.
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Odaka
authors.forename: Anne
authors.initials: A
authors.lastname: Loranger
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takizawa
authors.forename: Michel
authors.initials: M
authors.lastname: Ouellet
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Tremblay
authors.forename: Shigeo
authors.initials: S
authors.lastname: Murata
authors.forename: Akihito
authors.initials: A
authors.lastname: Inoko
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
authors.forename: Normand
authors.initials: N
authors.lastname: Marceau
mesh_terms: D000818:Animals; D004848:Epithelium / Q000033:anatomy & histology* / Q000378:metabolism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D053538:Keratin-18 / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D013950:Thymus Gland / Q000033:anatomy & histology*
chemical_list: D053538:Keratin-18; D053533:Keratin-8; C486595:Krt8 protein, mouse